446P - Capecitabine and streptozocin ± cisplatin for gastroenteropancreatic neuroendocrine tumours: predictors of long-term survival in the NET01 trial

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Anti-Cancer Agents & Biologic Therapy
Neuroendocrine Cancers
Presenter Tim Meyer
Citation Annals of Oncology (2016) 27 (6): 136-148. 10.1093/annonc/mdw369
Authors T. Meyer1, W. Qian2, J.W. Valle3, D. Talbot4, D. Cunningham5, N. Reed6, L. Wall7, J. Waters8, P. Ross9, A. Anthoney10, K. Sumpter11, N. Sarwar12, T. Crosby13, N. Begum2, G. Young2, R. Hardy2, P. Corrie14
  • 1Department Of Oncology, Royal Free London NHS Foundation Trust, NW3 2QG - London/GB
  • 2Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital University of Cambridge Hospitals, CB2 0QQ - Cambridge/GB
  • 3Department Of Medical Oncology, University of Manchester/The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 4Department Of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, OX3 7LE - Oxford/GB
  • 5Department Of Oncology, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 6Beatson Oncology Centre, Gartnavel General Hospital, G12 0YN - Glasgow/GB
  • 7Edinburgh Cancer Centre, Western General Hospital, EH4 2XU - Edinburgh/GB
  • 8Kent Oncology Centre, Maidstone Hospital, ME16 9QQ - Kent/GB
  • 9Department Of Oncology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 10St James's Institute Of Oncology, St James’s University Hospital, LS9 7TF - Leeds/GB
  • 11Northern Centre For Cancer Care, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, NE7 7DN - Newcastle upon Tyne/GB
  • 12Department Of Oncology, Southend University Hospitals NHS Foundation Trust, SS0 0RY - Southend/GB
  • 13Velindre Cancer Centre, Velindre NHS Trust, CF14 2TL - Cardiff/GB
  • 14Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, CB2 0QQ - Cambridge/GB

Abstract

Background

Cytotoxic chemotherapy for advanced, unresectable pancreatic and gastrointestinal foregut neuroendocrine tumours (GEPNETs) commonly comprises 5-fluorouracil (FU) plus streptozocin (S). The NET01 trial, conducted in the pre-kinase inhibitor era, recruited a broad spectrum of patients (pts) to investigate whether capecitabine (Cap) was an acceptable alternative to FU, with or without adding cisplatin (Cis). At median follow up 3.4 years, objective responses (primary endpoint) were reported as similar in the 2 arms, but CapSCis was more toxic. Final progression-free survival (PFS) and overall survival (OS) (secondary endpoints) as well as outcome predictors are now reported with longer follow up.

Methods

Pts with previously untreated advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly Cap 625mg/m2 twice daily orally, S 1·0g/m2 IV on day 1, ± Cis 70mg/m2 IV on day 1. Pts could receive the same treatment beyond 6 cycles if there was evidence of benefit. All pts were followed 12 weekly for a minimum of 5 years.

Results

Of 86 (44 CapS, 42 CapSCis) pts randomised, 16% had poorly differentiated histology. With long-term median follow-up of 8 years, 83 (97%) pts have progressed/died and 69 (80%) pts have died. The estimated median PFS was 11.1 months for CapS and 9·6 months for CapSCis (HR = 0.82, 95%CI: 0.53, 1.27). Median OS was 27 months for CapS and 26 months for CapSCis (HR = 0.97, 95%CI: 0.60, 1.56). Three and 5-year OS rates were 40% and 29%, with no difference between arms. Statistically significant factors predicting for OS were tumour Ki67 level, WHO grade and pt age. Addition of Cis to CapS did not appear to influence OS for high grade, poorly differentiated tumours, although numbers are small.

N Overall CapS CapSCis Median OS (yrs) Overall CapS CapSCis
Age (yrs)

Conclusions

PFS and OS were similar for the CapS ± Cis regimens. High patient age, tumour Ki67 and grade all predicted for poorer outcomes.

Clinical trial identification

Legal entity responsible for the study

Cambridge University Hospitals NHS Foundation Trust

Funding

UK NETwork and Cancer Research UK

Disclosure

J.W. Valle: Keocyt (honoraria for Advisory Board in 2010 and 2012) – this relates to streptozocin.

D. Cunningham: Research funding only to RMH from Amgen, AstraZeneca, Bayer, Celgene, Medimmune, Merrimack, Merck Serono, Sanofi. All other authors have declared no conflicts of interest.